Influenza virus is a worldwide public health problem. Influenza causes, on average, 20,000 deaths and many more thousands of hospitalizations annually in the United States alone (Palese and Garcia-Sastre, J. Clin. Invest., 110(1): 9-12, 2002). Vaccination is recommended for nearly half of the population of the United States (Couch, Ann. Intern. Med., 133: 992-998, 2000). Influenza also causes the death of thousands of domestic animals annually.
The effectiveness of currently available vaccines depends on the degree to which the vaccine antigens match those of the circulating influenza strains. Immune responses to an antigen of a particular type of influenza may be poorly cross-reactive with the antigen encoded by a second type of influenza. Influenza viruses have the tendency to undergo antigenic changes, complicating efforts to produce effective vaccines. Antigenic shift, which occurs when genes from different influenza types reassort in infected hosts, is one mechanism by which dramatic antigenic variation occurs. Antigenic shift occurs in influenza A types, which circulate among humans and animals. Influenza B types are more restricted to humans and are not thought to undergo antigenic shift (Palese and Garcia-Sastre, J. Clin. Invest., 110(1): 9-12, 2002). Antigenic drift is a second, less drastic mechanism, in which viral genes accumulate mutations over time. Both types of antigenic variation increase the difficulty of generating vaccines effective for protection against a broad range of influenza strains.